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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/F919    most recent 00265.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hill, W. G. Articles by Zeidel, M. L. Search for Related Content PubMed PubMed Citation Articles by Hill, W. G. Articles by Zeidel, M. L.

Studies on localization and function of annexin A4a within urinary bladder epithelium using a mouse knockout model

¹Division of Matrix Biology, ²Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts; ³Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and ⁴Department of Molecular Oncogenesis, University of Cincinnati Genome Research Institute, Cincinnati, Ohio

Submitted 8 June 2007 ; accepted in final form 29 January 2008

Annexin A4 (anxA4) is a member of the Ca²⁺-dependent membrane-binding family of proteins implicated in the regulation of ion conductances, Ca²⁺ homeostasis, and membrane trafficking. We demonstrate, in mice, that annexins 1–6 are present in whole bladder and exhibit differential expression in the urothelium. An anxA4a-knockout (anxA4a^–/–) mouse model shows no protein in the urothelium by immunofluorescence and immunoblotting. In wild-type bladders, anxA4a in umbrella cells showed uniform cytoplasmic staining and some association with the nuclear membrane. Application of a hydrostatic pressure to bladders mounted in Ussing chambers resulted in redistribution of anxA4a from cytoplasm to cellular boundaries in the basal and intermediate cells but not in superficial umbrella cells. We hypothesized that anxA4a might be important for barrier function or for stretch-activated membrane trafficking. To test these hypotheses, we conducted a series of functional and morphological analyses on bladders from control and anxA4a^–/– animals. The transepithelial resistances, water permeabilities, and urea permeabilities of anxA4a^–/– bladders were not different from controls, indicating that barrier function was intact. Membrane trafficking in response to hydrostatic pressure as measured by capacitance increases was also normal for anxA4a^–/– bladders. Cystometrograms performed on live animals showed that voiding frequency and intrabladder pressures were also not different. There were no differences in bladder surface morphology or cellular architecture examined by scanning and transmission electron microscopy, respectively. We conclude that loss of anxA4 from the urothelium does not affect barrier function, membrane trafficking, or normal bladder-voiding behavior.

permeability; barrier; trafficking